Optical isomers of an iloperidone metabolite

Abstract

The present invention relates to novel isomers of a metabolite of Iloperidone, their preparation, their use as pharmaceuticals and pharmaceutical compositions containing them.

1. A pharmaceutical composition, in the form of capsules, tablets, or injectable solutions or suspensions, for use as a pharmaceutical in the treatment of a psychotic disorder in a human consisting essentially of an antipsychotic effective amount of (R)-1-[4-{3-[4-(6-fluoro-benzo(d)isoxazol-3-yl)-piperidin-1-yl]propoxy}-3-methoxy-phenyl]-ethanol or a pharmaceutically acceptable salt thereof and a pharmaceutical carrier or diluent. 
     
     
       2. The pharmaceutical composition of  claim 1  for treating a psychotic disorder in a human consisting essentially of an antipsychotic effective amount of (R)-1-[4-{3-[4-(6-fluoro-benzo(d)isoxazol-3-yl)-piperidin-1-yl]propoxy}-3-methoxy-phenyl]ethanol prepared by enantioselective reduction of iloperidone and a pharmaceutical carrier or diluent. 
     
     
       3. The pharmaceutical composition of  claim 2 , wherein the reduction is effected by contact of iloperidone with an optically-active borane complex of formula IV 
       
         
           
           
               
               
           
         
       
     
     
       4. A method for treating a psychotic disorder in a human subject in need of such treatment, the method comprising orally or parenterally administering to the subject a therapeutically effective amount of (R)-1-[4-{3-[4-(6-fluoro-benzo(d)isoxazol-3-yl)-piperidin-1-yl]propoxy}-3-methoxy-phenyl]-ethanol or a pharmaceutically acceptable salt thereof admixed with at least one pharmaceutical carrier. 
     
     
       5. The pharmaceutical composition of  claim 1  in the form of a capsule or tablet. 
     
     
       6. The pharmaceutical composition of  claim 1  in the form of a capsule, tablet, or injectable solution or suspension consisting essentially of about 1 to about 500 mg of (R)-1-[4-{3-[4-(6-fluoro-benzo(d)isoxazol-3-yl)-piperidin-1-yl]propoxy}-3-methoxy-phenyl]-ethanol and a pharmaceutical carrier or diluent. 
     
     
       7. The pharmaceutical composition of  claim 1  in unit dosage form consisting essentially of 0.25 to about 25 mg of (R)-1-[4-{3-[4-(6-fluoro-benzo(d)isoxazol-3-yl)-piperidin-1-yl]propoxy}-3-methoxy-phenyl]-ethanol and a pharmaceutical carrier or diluent. 
     
     
       8. The method of  claim 4 , wherein the pharmaceutical composition is in the form of a capsule or tablet. 
     
     
       9. The method of  claim 4 , wherein the pharmaceutical composition is in the form of a capsule, tablet, or injectable solution or suspension consisting essentially of about 1 to about 500 mg of (R)-1-[4-{3-[4-(6-fluoro-benzo(d)isoxazol-3-yl)-piperidin-1-yl]propoxy}-3-methoxy-phenyl]ethanol and a pharmaceutical carrier or diluent. 
     
     
       10. The method of  claim 4 , wherein the pharmaceutical composition is in unit dosage form consisting essentially of 0.25 to about 25 mg of (R)-1-[4-{3-[4-(6-fluoro-benzo(d)isoxazol-3-yl)-piperidin-1-yl]propoxy}-3-methoxy-phenyl]ethanol and a pharmaceutical carrier or diluent.